Tinnitus-frequency specific activity and connectivity: A MEG study.

Tinnitus pathophysiology has been associated with an atypical cortical network that involves functional changes in auditory and non-auditory areas. Numerous resting-state studies have replicated a tinnitus brain network to be significantly different from healthy-controls. Yet it is still unknown whether the cortical reorganization is attributed to the tinnitus frequency specifically or if it is frequency-irrelevant. Employing magnetoencephalography (MEG), the current study aimed to identify frequency-specific activity patterns by using an individual tinnitus tone (TT) and a 500 Hz-control tone (CT) as auditory stimuli, across 54 tinnitus patients. MEG data were analyzed in a data-driven approach employing a whole-head model in source space and in sources' functional connectivity. Compared to the CT, the event related source space analysis revealed a statistically significant response to TT involving fronto-parietal regions. The CT mainly involved typical auditory activation-related regions. A comparison of the cortical responses to a healthy control group that underwent the same paradigm rejected the alternative interpretation that the frequency-specific activation differences were due to the higher frequency of the TT. Overall, the results suggest frequency-specificity of tinnitus-related cortical patterns. In line with previous studies, we demonstrated a tinnitus-frequency specific network comprising left fronto-temporal, fronto-parietal and tempo-parietal junctions.

Comparing pure tone and narrow band noise to measure tonal tinnitus pitch-match frequency.

Tinnitus assessment is a precursor for individualized treatment and outcome measurement. In the recent years, several studies proposed two-alternative forced choice (2AFC) recursive matching as a method to determine tinnitus pitch-match frequency in a standardized reliable manner. Currently, pure tones are used as comparison stimuli to assess pitch-match frequency. In this study, we investigated the psychometric quality of the method comparing different sound types. We measured 20 chronic tinnitus patients in 2 runs on 3 days. To assess pitch-match frequency, we used 2AFC recursive matching and compared results between pure tones and narrow band noise (NBN). Test-retest reliability between runs and across sound types was high (α>0.9) and increased across days. Perceived matching difficulty and time to completion decreased over repetitions. Importantly, the difference of matched frequencies (DMF) between runs was significantly less for NBN. When patients matched the spectral bandwidth of a test tone to their tinnitus, consistency was high (α=0.86) and no patient indicated continuously a pure tone. In conclusion, we recommend using NBN sounds in 2AFC recursive matching to assess pitch-match frequency as a standardized reliable method. Such a procedure could be offered as smartphone-based application to monitor tinnitus symptomatology for individualized assessment and treatment outcome.

One Step Closer towards a Reliable Tinnitus Pitch-Match Frequency Determination Using Repetitive Recursive Matching.

INTRODUCTION: The determination of the tinnitus pitch-match (PM) frequency is not straightforward but an important audiological assessment recommended for clinical and research purposes. We evaluated repetitive recursive matching using an iPod-based matching procedure as a method to estimate a patient's PM frequency without audiometric equipment. METHODS: One hundred and seventeen patients with chronic tonal tinnitus (uni- and bilateral tinnitus) measured their tinnitus in 10 sessions using a self-administered automated iPod-based procedure comprising a recursive 2 interval forced-choice test. RESULTS: Mean SD of the PM frequency of all participants across sessions was 0.41 octaves. The internal consistency measured by Cronbach's α was very high (0.8->0.95). As an example, 7 PMs obtained excellent internal consistency (α = 0.93). The exclusion of the first and/or second session led to more definite PMs with a decreased SD. Outliers were identified by PMs departing 2 SDs (i.e., 0.94 octaves) from the mean variability (n = 5). CONCLUSION: Repetitive recursive matching together with recommendations for the exclusion of initial and redundant sessions as well as outlier identification and treatment can enable a reliable estimation of the PM frequency.

Auditory Categorization of Man-Made Sounds Versus Natural Sounds by Means of MEG Functional Brain Connectivity.

Previous neuroimaging studies have shown that sounds can be discriminated due to living-related or man-made-related characteristics and involve different brain regions. However, these studies have mainly provided source space analyses, which offer simple maps of activated brain regions but do not explain how regions of a distributed system are functionally organized under a specific task. In the present study, we aimed to further examine the functional connectivity of the auditory processing pathway across different categories of non-speech sounds in healthy adults, by means of MEG. Our analyses demonstrated significant activation and interconnection differences between living and man-made object sounds, in the prefrontal areas, anterior-superior temporal gyrus (aSTG), posterior cingulate cortex (PCC), and supramarginal gyrus (SMG), occurring within 80-120 ms post-stimulus interval. Current findings replicated previous ones, in that other regions beyond the auditory cortex are involved during auditory processing. According to the functional connectivity analysis, differential brain networks across the categories exist, which proposes that sound category discrimination processing relies on distinct cortical networks, a notion that has been strongly argued in the literature also in relation to the visual system.

Maladaptive alterations of resting state cortical network in Tinnitus: A directed functional connectivity analysis of a larger MEG data set.

The present study used resting state MEG whole-head recordings to identify how chronic tonal tinnitus relates to altered functional connectivity of brain's intrinsic cortical networks. Resting state MEG activity of 40 chronic tinnitus patients and 40 matched human controls was compared identifying significant alterations in intrinsic networks of the tinnitus population. Directed functional connectivity of the resting brain, at a whole cortex level, was estimated by means of a statistical comparison of the estimated phase Transfer Entropy (pTE) between the time-series of cortical activations, as reconstructed by LORETA. As pTE identifies the direction of the information flow, a detailed analysis of the connectivity differences between tinnitus patients and controls was possible. Results indicate that the group of tinnitus patients show increased connectivity from right dorsal prefrontal to right medial temporal areas. Our results go beyond previous findings by indicating that the role of the left para-hippocampal area is dictated by a modulation from dmPFC; a region that is part of the dorsal attention network (DAN), as well as implicated in the regulation of emotional processing. Additionally, this whole cortex analysis showed a crucial role of the left inferior parietal cortex, which modulated the activity of the right superior temporal gyrus, providing new hypotheses for the role of this area within the context of current tinnitus models. Overall, these maladaptive alterations of the structure of intrinsic cortical networks show a decrease in efficiency and small worldness of the resting state network of tinnitus patients, which is correlated to tinnitus distress.

Choice of test stimulus matters for pitch matching performance: Comparison between pure tone and narrow band noise.

Chronic tinnitus, a symptom of high prevalence, is a persistent hearing sensation in the absence of an external sound source. Recent electrophysiological studies indicate that tinnitus generation is to a high degree the result of maladaptive plasticity in the central auditory pathway. The pitch of the tinnitus sensation can be assessed by performing a pitch matching procedure. In the most frequent "tonal tinnitus" type pure tones are used as test stimuli. However, in the case of tonal tinnitus not a single malfunctioning neuron, but rather a population of neighbouring neurons is involved in the generation process of tinnitus and patients typically perceive their tinnitus as a sound having a prominent centre frequency with some spectral extent. Thus, the question arises, why not to use narrow band noise (NBN) instead of pure tones as test stimuli in pitch matching procedures? To investigate this, we first evaluated the pitch matching performance of healthy subjects. In a recursive two alternative choice testing, driven by a computer based automated procedure, the subjects were asked to match the pitch of two sounds. In a crosswise design, NBNs and pure tones were used both as target and as test stimuli. We were able to show that across all four possible combinations the pitch matching performance was least favourable when a sinusoidal sound had to be matched to an NBN target. Even though matching two sinusoidal sounds results in the lowest error, considering that the tinnitus percept typically includes some spectral extent, an NBN should be preferably used as a test stimulus against a pure tone.